Other entities represented in this entry:
ORPHA: 79189, 912; DO: 0080486;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 1q23.2 | Peroxisome biogenesis disorder 12A (Zellweger) | 614886 | Autosomal recessive | 3 | PEX19 | 600279 |
A number sign (#) is used with this entry because this form of Zellweger syndrome (PBD12A) is caused by homozygous mutation in the PEX19 gene (600279) on chromosome 1q23.
Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome resulting from disordered peroxisome biogenesis. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life (summary by Steinberg et al., 2006).
For a complete phenotypic description and a discussion of genetic heterogeneity of Zellweger syndrome, see 214100.
Individuals with PBDs of complementation group 14 (CG14, equivalent to CGJ) have mutations in the PEX19 gene. For information on the history of PBD complementation groups, see 214100.
Mohamed et al. (2010) studied a female infant, born of consanguineous Saudi parents, with Zellweger syndrome, The patient had neonatal hypotonia, poor growth, and subtle dysmorphic features, including cranial asymmetry, triangular face, low hairline, open fontanels, and broad nasal bridge. Laboratory studies showed elevated liver enzymes, hyperbilirubinemia, and a very long chain fatty acid (VLCFA) profile consistent with a PBD. Brain imaging showed cerebral atrophy, cortical changes, and diffuse demyelination. There was a complete absence of peroxisomes in patient fibroblasts. The patient had a severe clinical course, complicated by global developmental delay, refractory seizures, renal tubular defect, multiple gallstones, and recurrent hospitalizations. She died of sepsis at age 16 months.
Kinoshita et al. (1998) identified complementation group J (CGJ) from patients with Zellweger syndrome. Two Chinese hamster ovary cell mutants were also found to belong to this group. In no CGJ mutant cell were peroxisomal ghosts found.
Matsuzono et al. (1999) identified a homozygous 1-bp insertion in the PEX19 gene (600279.0001) in a patient with Zellweger syndrome of complementation group J.
Mohamed et al. (2010) identified a homozygous frameshift mutation in the PEX19 gene (600279.0002) in a female infant with Zellweger syndrome.
Kinoshita, N., Ghaedi, K., Shimozawa, N., Wanders, R. J. A., Matsuzono, Y., Imanaka, T., Okumoto, K., Suzuki, Y., Kondo, N., Fujiki, Y. Newly identified Chinese hamster ovary cell mutants are defective in biogenesis of peroxisomal membrane vesicles (peroxisomal ghosts), representing a novel complementation group in mammals J. Biol. Chem. 273: 24122-24130, 1998. [PubMed: 9727033] [Full Text: https://doi.org/10.1074/jbc.273.37.24122]
Matsuzono, Y., Kinoshita, N., Tamura, S., Shimozawa, N., Hamasaki, M., Ghaedi, K., Wanders, R. J. A., Suzuki, Y., Kondo, N., Fujiki, Y. Human PEX19: cDNA cloning by functional complementation, mutation analysis in a patient with Zellweger syndrome, and potential role in peroxisomal membrane assembly. Proc. Nat. Acad. Sci. 96: 2116-2121, 1999. [PubMed: 10051604] [Full Text: https://doi.org/10.1073/pnas.96.5.2116]
Mohamed, S., El-Meleagy, E., Nasr, A., Ebberink, M. S., Wanders, R. J. A., Waterham, H. R. A mutation in PEX19 causes a severe clinical phenotype in a patient with peroxisomal biogenesis disorder. Am. J. Med. Genet. 152A: 2318-2321, 2010. [PubMed: 20683989] [Full Text: https://doi.org/10.1002/ajmg.a.33560]
Steinberg, S. J., Dodt, G., Raymond, G. V., Braverman, N. E., Moser, A. B., Moser, H. W. Peroxisome biogenesis disorders. Biochim. Biophys. Acta 1763: 1733-1748, 2006. [PubMed: 17055079] [Full Text: https://doi.org/10.1016/j.bbamcr.2006.09.010]